Interferon-λ1 induces G1 phase cell cycle arrest and apoptosis in gastric carcinoma cells in vitro

Abstract

The aim of the present study was to examine the potential antitumor action of IFN-λ1 in human gastric carcinoma cell lines and the possible interaction between IFN-λ1 and human gastric carcinoma cells. Gastric carcinoma HGC-27 and SGC-7901 cells were treated with IFN-λ1 (0, 10, 100, 1000 ng/ml) for 48 h. Cytotoxicity was examined using an MTT method. Cell cycle distribution was examined using propidium iodide staining. Apoptosis was examined using the Annexin V-FITC/PI apoptosis kit. By using flow cytometry and JC-1 probe, the mitochondrial membrane potential of cells following treatment with IFN-λ1 was also examined. Expression levels of representative apoptosis-related proteins were evaluated by western blot analysis. IFN-λ1 inhibited the proliferation of gastric carcinoma cells in a concentration- dependent manner. IFN-λ1 increased the accumulation of cells in the sub-G0 phase and arrested the cells in the G1 phase. Exposure to IFN-λ1 decreased the mitochondrial membrane potential and increased apoptosis. Moreover, IFN-λ1 exposure upregulated the expression of p21, p27 and Bax, downregulated the expression of Bcl-2, increased the release of cytochrome c and apoptosis-inducing factor (AIF) and activated caspase-3 and caspase-9. In conclusion, IFN-λ1 inhibits the proliferation of gastric carcinoma cells by arresting the cells in the G1 phase and by inducing mitochondrial-mediated apoptosis.